Many patients require long-term, regular dosing with drugs or pharmaceutical substances, including substances for pain control. Effective treatment often necessitates the ingestion of multiple tablets per day. Compliance with this dosing scheme is often difficult. Furthermore, enteral drug delivery is sometimes poorly tolerated or prohibited in patients with particular indications. In addition, oral tablets may be subject to abuse or other illicit use. Oral and sublingual delivery can result in plasma concentrations of drug peaking quickly and dropping steeply. Continuous parenteral delivery of drug substances is expensive, cumbersome and dependent on the availability of refrigeration, catheters, pumps and trained personnel. These methods can result in poor patient compliance with dosing regimes. Thus, there is a need for devices which regularly dose patients with drug substances.
Implantable devices may be used for drug delivery. These devices can produce long-term delivery of drugs, ensuring compliance independent of the patient, maintaining stable plasma levels of medication and reducing the likelihood of abuse or diversion.
Continuous release of a compound in vivo over an extended duration may be achieved via implantation of a device containing the compound encapsulated in a polymeric matrix. Examples of implantable polymeric devices for continuous drug release are described in, e.g., U.S. Pat. Nos. 4,883,666; 5,114,719; and 5,601,835. Patel et al. U.S. Patent Application Publication Nos. 2004/0033250, 2007/0275031, and 2008/0026031, and Kleppner et al. 2006 J. Pharm. Pharmacol. 58:295-302 describe an implantable device comprising buprenorphine blended with ethylene vinyl acetate (EVA copolymer). Patel et al. U.S. Patent Application Publication No. 2005/0031668 describes an implantable polymeric device for sustained release of nalmefene. Patel et al. U.S. Patent Application Publication No. 2005/0031667 describes an implantable polymeric device for sustained release of dopamine agonists. Additional drug delivery devices include stents coated with compositions comprising drugs. Various devices and coatings are described in U.S. Pat. No. 6,506,437 to Harish; U.S. Pat. No. 7,364,748 to Claude and U.S. Pat. No. 7,384,660 to Hossainy. U.S. Pat. No. 3,625,214 describes a drug-delivery device for prolonged drug delivery, fabricated in a spiral or “jellyroll” fashion. U.S. Pat. No. 3,926,188 describes a three-layer laminate drug dispenser comprising a core lamina of a crystalline drug of low water solubility dispersed in a polymer matrix, interposed between outer laminas made of a drug release rate controlling polymer. U.S. Pat. No. 5,683,719 describes a controlled release composition comprising an extruded core of active material and excipients, the core being coated in a water insoluble coating.
Implantable devices are inserted subcutaneously in areas of the body, and may be subject to physical damage. Kleppner et al. 2006 J. Pharm. Pharmacol. 58:295-302 described breakage of devices within the bodies of treated dogs. Implantable devices comprising EVA (ethyl vinyl acetate copolymer) and buprenorphine (for treatment of opioid dependence) were inserted subcutaneously in the backs of test dogs. 70% of the implants had broken within 10 months. Drug delivery was estimated to increase by 5% in implants that broke into two pieces, and 10% in implants that broke into three pieces. Thus, breakage of implantable devices would interfere with the regulated dosing and delivery of drug substances. Breakage of the implantable devices may also result in jagged device edges which could cause tissue damage and pain to the patient. Finally, breakage of the implantable devices seriously complicates removal of the device, as it may be difficult to extract the broken pieces without causing damage to the surrounding tissue.
There is a need for implantable devices which are not subject to breakage within the body of the patient.